HUMAN C5A AND C5A ANALOGS AS PROBES OF THE NEUTROPHIL C5A RECEPTOR
HUMAN C5A AND C5A ANALOGS AS PROBES OF THE NEUTROPHIL C5A RECEPTOR
复制标题
DOI：
10.1016/0161-5890(80)90067-x
复制
发表时间：
1980-01-01
影响因子：
3.6
通讯作者：
HUGLI, TE
中科院分区：
文献类型：
--
作者：
CHENOWETH, DE;HUGLI, TE
人中性粒细胞趋化反应的定量评估和免疫学证据表明，人C5a和/或其生理等效物C5ades Arg'充当补体激活血清中的主要趋化因子。 C5a 及其 des Arg74 衍生物均能够促进定向细胞迁移以及溶酶体酶释放。在不存在外来人血清蛋白的情况下，通过“琼脂糖下方法”评估中性粒细胞趋化性。发现 C5a 的活性比 C5ades Arg 高约 10 至 30 倍。当评估每个因子促进经细胞松弛素 B 处理的中性粒细胞分泌嗜天青颗粒酶的能力时，获得了定量相似的结果。 C5a 结构类似物 C5a-(1-69) 缺少母体分子 C 端部分的 5 个残基，以及模拟 C5a C 端线性序列的合成五肽-甲硫氨酰-l-谷氨酰胺酰-l-亮氨酰甘氨酰-l-精氨酸 (Chenowethet al., 1979a)，在单独或组合检查时发现缺乏生物活性。这些发现意味着 C5a 的 C 末端部分对于调节中性粒细胞上的配体-受体相互作用发挥着重要作用。基于这些观察结果，提出了人类 C5a 与中性粒细胞 C5a 受体相互作用的概念模型。我们假设除了分子 C 端区域包含的“激活”位点外，C5a 还拥有一个内部“识别”位点。
Quantitative assessment of the human neutrophil chemotactic response and immunologic evidence demonstrate that human C5a and/or its physiological equivalent, C5ades Arg'serves as the predominant chemotactic factor in complement activated serum. Both C5a and its des Arg74 derivative are capable of promoting directed cellular migration as well as lysosomal enzyme release. When neutrophil chemotaxis is assessed by an ‘under agarose methodology’, in the absence of extraneous human serum proteins. C5a is found to be some 10- to 30-fold more active than C5ades ArgQuantitatively similar results are obtained when each factor is assessed for its ability to promote secretion of azurophilic granular enzymes from cytochalasin B-treated neutrophils. The C5a structural analog C5a-(1–69), lacking five residues of the C-terminal portion of the parent molecule, and a synthetic pentapeptidel-methionyl-l-glutaminyl-l-leucylglycyl-l-arginine, which mimics the C-terminal linear sequence of C5a (Chenowethet al., 1979a), are found to be devoid of biological activity when examined either-alone or in combination. These findings imply that the C-terminal portions of C5a contribute importantly to modulating ligand-receptor interactions on neutrophils. Based on these observations, a conceptual model of the interaction of human C5a with the neutrophil C5a receptor is proposed. We hypothesize that C5a possesses an internal ‘recognition’ site in addition to the ‘activation’ site contained in the C-terminal region of the molecule.